Preconditioning with bright light evokes a protective response against light damage in the rat retina.
Constant exposure to bright light induces photoreceptor degeneration and at the same time upregulates the expression of several neurotrophic factors in the retina. At issue is whether the induced neurotrophic factors protect photoreceptors. We used a preconditioning paradigm to show that animals preconditioned with bright light became resistant to subsequent light damage. The preconditioning consisted of a 12-48 hr preexposure, followed by a 48 hr "rest phase" of normal cyclic lighting. The greatest protection was achieved by a 12 hr preexposure. Preconditioning induces a prolonged increase in two endogenous neurotrophic factors: basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). It also stimulates the phosphorylation of extracellular signal-regulated protein kinases (Erks) in both photoreceptors and Müller cells. These findings indicate that exposure to bright light initiates two opposing processes: a fast degenerative process that kills photoreceptors and a relatively slower process that leads to the protection of photoreceptors. The extent of light damage, therefore, depends on the interaction of the two processes. These results also suggest a role of endogenous bFGF and CNTF in photoreceptor protection and the importance of Erk activation in photoreceptor survival.
Liu
C
C
Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Peng
M
M
Laties
A M
AM
Wen
R
R
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D003213:Conditioning, Psychological / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008027:Light; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000502:physiology / Q000528:radiation effects; D011832:Radiation Injuries / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D013997:Time Factors
D020934:Ciliary Neurotrophic Factor; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases